Rediscovery of Nefopam for the Treatment of Neuropathic Pain

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non-sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.

Cancer Pain Management-Nonopoid Analgesics

Cancer pain patients have various diagnosis, stage of disease, response to pain, and treatments and individualized treatment methods are thus needed. Use of Nonopioid analgesics is the first step treatment (according to WHO ladder) for mild to moderate pain, and may be useful for second or third step treatments when combined with weak or strong opioids to reduce side effects of opioids and to create synergy between the two drugs. Acetaminophen and nonsteroidal antiinflammatory drugs(NSAIDs) are also nonopioid analgesics. NSAIDs have a ceiling effect, along with antipyretic, analgesic and antiinflammatory effects, while not producing physical and psychological dependence. Adverse effects of NSAIDs include gastrointestinal hemorrhage, coagulopathy, and deterioration of renal function.

Current pharmacological management of chronic pain

Chronic pain is associated with disabling physical and emotional symptoms. Patients with chronic pain utilize more health services, have an impaired sense of well-being and frequently experience anxiety or depression. Unfortunately, treatment for chronic pain is not always correctly targeted, which leads to a reduced quality of life. Treatment of chronic pain involves a comprehensive approach using medication and functional rehabilitation. The usual approach for mild to moderate pain is to start with nonopioid analgesics. Also, trying antidepressant drugs for sleep loss and gabapentin for neuropathic pain or fibromyalgia is appropriate. For moderate to severe chronic pain, opioid analgesics can be used without any serious side effects if adequately used at the right dosage. It is important to provide guidance on the safe use of analgesics and other psychoactive drugs. Dosing of acetaminophen should be limited to avoid liver toxicity, and topical analgesics are preferred for focal pain. Full-dose nonsteroidal anti-inflammatory drugs should not be used for more than short periods, in order to avoid gastrointestinal, renal, and cardiovascular complications. Mechanisms of analgesia, drug selection, and recommendations for clinical usage for the management of chronic pain are reviewed in this paper.